Title 15. CHEMOTHERAPY OF MALARIA.pdf ✅

PHARMD GURU Page 1 Malaria is a protozoal infection caused by genus Plasmodium and transmitted to humans by the infected female Anopheles mosquito. The species of malarial parasites are Plasmodium vivax, Plasmodium ovale, Plasmodium malariae, P. falciparum and Plasmodium knowlesi. The incidence of malaria is increasing due to the resistance of vectors to insecticides and drug-resistant parasites. In India, P. vivax and P. falciparum are common. CHEMOTHERAPY OF MALARIA
PHARMD GURU Page 2 CLASSIFICATION: 1. CHEMICAL CLASSIFICATION: a) 4-Aminoquinolines: Chloroquine, amodiaquine, piperaquine b) 8-Aminoquinolines: Primaquine, tafenoquine c) Quinoline methanol: Mefloquine d) Alkaloids: Quinine, quinidine e) Antifolates: Pyrimethamine, sulphadoxine, dapsone, proguanil f) Antibiotics: Doxycycline, clindamycin g) Hydroxynaphthoquinone: Atovaquone h) Artemisinins: Artemisinin, artemether, artesunate, arteether, arterolane, dihydroartemisinin i) Aryl alcohol: Lumefantrine 2. CLINICAL CLASSIFICATION: (a) This classification is based on the stage of the parasite they affect (Table 11.21 and Fig. 11.15). 1) Tissue schizontocidal agents: These act on primary (pre-erythrocytic) and latent (hypnozoites) tissue forms in the liver, e.g. primaquine, and are effective against both forms; atovaquone and proguanil act on primary form. 2) Blood schizontocidal agents: These act on erythrocytic stage of Plasmodium and, thereby, terminate the clinical attack.  Rapid acting and high-efficacy agents, e.g. chloroquine, artemisinin derivatives, quinine, mefloquine, atovaquone, amodiaquine and lumefantrine.  Slow-acting and low-efficacy agents, e.g. proguanil, pyrimethamine " sulphadoxine and clindamycin; used always in combination with rapid- acting agents. 3) Gametocidal agents: These kill gametocytes of plasmodia in blood, e.g. artemisinin and primaquine (active against all species); chloroquine and quinine (vivax). They reduce transmission to mosquitoes.
PHARMD GURU Page 3 (b) Based on clinical indication for use (clinical utility) 1) Drugs used for causal prophylaxis, i.e. pre-erythrocytic stage of Plasmodium in liver, e.g. proguanil and primaquine. Primaquine is effective against all species but not used due to its toxic potential. Proguanil is effective mainly for P. falciparum. 2) Drugs for suppressive prophylaxis: Suppress erythrocytic phase, thus clinical attack of malaria is prevented – clinical disease is not manifested, e.g. chloroquine, mefloquine and doxycycline. 3) Drugs used for clinical cure: These agents act on erythrocytic stages of malarial parasite to terminate the clinical attack. They are rapid-acting and slow-acting blood schizontocidal agents. 4) Drugs used to prevent relapse: These drugs act on the latent tissue forms (hypnozoites) of P. vivax and P. ovale which cause relapse, e.g. primaquine and tafenoquine. Radical cure of P. vivax and P. ovale is achieved with the use of a blood schizontocidal agent along with primaquine which acts on latent tissue forms (hypnozoites) to prevent relapse. 5) Drugs used to prevent the transmission of infection to Anopheles mosquito (gametocidal agents): Primaquine has gametocidal effect against all species of plasmodia that infect humans.
PHARMD GURU Page 4 INDIVIDUAL DRUGS IN CHEMICAL CLASSIFICATION a) 4-AMINOQUINOLINES: CHLOROQUINE: Chloroquine is a 4-aminoquinoline. It is very effective and rapidly acting blood schizontocide against P. vivax, P. ovale, P. malariae, chloroquine-sensitive strains of P. falciparum and P. knowlesi. It has no activity against liver forms (pre-erythrocytic and hypnozoites). MECHANISM OF ACTION: Chloroquine is a basic drug, which is taken up by the acidic food vacuoles of susceptible plasmodia and inhibits the conversion of haeme to haemozoin. The ‘drug–haeme’ complex is toxic and kills the parasite. Resistance to chloroquine is common with P. falciparum. In the acidic vacuole of plasmodia: PHARMACOKINETICS: Chloroquine is commonly administered by oral route. It is well absorbed after oral and parenteral administration. It has strong affinity for melanin-containing tissues. It gets rapidly distributed to tissues (extensive tissue binding); therefore, to achieve an effective therapeutic plasma concentration, a loading dose is used during treatment of malaria. It gets concentrated in liver, spleen, kidney, lungs, skin, etc. Chloroquine is metabolized in the liver and slowly excreted in urine. ADVERSE EFFECTS AND CONTRAINDICATIONS: Chloroquine in antimalarial doses may cause nausea, vomiting, skin rashes, itching, headache and visual disturbances. Parenteral administration can cause hypotension, confusion, cardiac arrhythmias, convulsions and even cardiac arrest. Prolonged